Neurology: Epilepsy Flashcards
Remind yourself of the main excitatory and inhibitory neurotransmitters in brain and state which receptor they act on
- Excitatory: glutamate via NMDA receptor
- Inhibitory: GABA via GABAa receptor
What are seizures?
Transient occurrence of signs and symptoms due to episodes of abnormal electrical activity in the brain
There are many other causes of seizures, other than epilepsy, state some other causes
- Febrile convulsions (young children)
- Alcohol withdrawal
- Pseudoseizures/psychogenic non-epileptic seizures
- Raised ICP e.g. following head trauma, infection etc…
- Metabolic disturbance e.g. hypoglycaemia
Seizures are classified based on what 3 key features?
Describe the classification of seizures
Classified based on:
- Where seizure began (generalised or focal onset)
- Level of awareness during seizure (consciousness always lost in generalised onset)
- Other features of seizure (broadly split into motor and non-motor and then into different subtypes based on features)
What do we mean by generalised onset seizures?
What do we mean by focal onset seizures?
Generalised
- Abnormal electrical activity starts in both sides of brain
- Pts always lose consciousness
- Affects both sides of body
Focal
- Abnormal electrical activity starts in one side of brain (has potential to spread to other side but starts in one side only)
- Level of awareness/consciousness can vary
Describe the typical presentation tonic clonic seizures
- Often starts with tonic phase (increased muscle tone)
- Followed by clonic phase (rapid, rhythmic jerking)
- May have associated tongue biting, incontinence, cyanosis
Describe the typical presentation of tonic seizures
- Increase in muscle tone
- Usually happen during sleep
- Usually short in duration (<30 secs)
- Pt may fall to ground if stood up when it occurs
Describe the typical presentation of absence seizures
- Person blanks out
- Generalised onset (so consciousness always lost)
- Two subtypes:
- Typical: last <10 seconds, eyelids may flutter
- Atypical up to 20 seconds or more, slower/less clear onset and offset, repetitive blinking, altered muscle tone, lip smacking, hand motions
Describe typical presentation of atonic seizures
- Loss of muscle tone
- If standing pt often falls to ground
- Typically <15 seconds
Describe the typical presentation of myoclonic seizures
- Sudden, short-lasting jerks (may be mild or forceful making you drop something etc…)
- Usually only last 1-2 seconds but may have clusters
Previously, the following phrases were used; explain what each is referring to:
- Grand mal
- Petit mal
- Simple partial
- Complex partial
- Grand mal: generalised tonic-clonic seizure
- Petit mal: typical absence seizure
- Simple partial: focal aware seizure
- Complex partial: focal impaired awareness seizure
What is Jacksonian march/seizure?
- Kind of a simple partial seizure
- The characteristic features of Jacksonian march are
- It only occurs on one side of the body
- It progresses in a predictable pattern from twitching or a tingling sensation or weakness in a finger, a big toe or the corner of the mouth, then marches over a few seconds to the entire hand, foot or facial muscles.
What specific questions should you include when taking a history of someone who blacked out and may have had a seizure?
Before event
- What were they doing?
- Lightheaded, dizzy, chest pain, palpitations, aura
- Eaten, drank, taken medication etc…
- Did anyone see them? How did they look (ask about colour of skin etc…)
During event
- Consciousness lost or not
- Any falls/potential injuries
- How long
- Did anyone see them? What did they look like (ask about e.g. cyanosis)? What did they do?
- Tongue biting (lateral tongue biting more specific to epilepsy), incontinence
After event
- Did they recall what happened?
- Able to get themselves up
- Any injuries
- Any post-ictal period (confusion, drowsiness, tired etc..)- how long?
- Did anyone see them? What did they look like?
Focal seizures start in one side of/hemisphere of brain; state some features in history that may allow you to further localisation the location of a focal seizure
What is epilepsy?
A condition in which person has a tendency toward recurrent seizures which are unprovoked by a systemic or severe neurological insult
*Idea that anyone can have seizures, epilepsy is the tendancy towards having seizures even when there is no systemic or severe neurological trigger.
Discuss the pathology of seizures in terms of neurotransmitters
A seizure is the clinical manifestation of abnormal and excessive excitation and synchronisation of a group of neurones within the brain. There may be loss of inhibitory (GABA mediated) signals or too strong an excitatory signals (NMDA/glutamate)
What is epilepsy?
A condition in which person has a tendancy toward recurrent seizures which are unprovoked by a systemic or severe neurological insult
*Idea that anyone can have seizures, epilepsy is the tendancy towards having seizures even when there is no systemic or severe neurological trigger.
What are reflex seizures?
Seizures brought on by a particular stimulus e.g. flashing lights HOWEVER none of the stimuli are classed as a severe neurological insult therefore the seizure is still classed as unprovoked and it is still epilepsy
How many seizures do you need to have had to be diagnosed with epilepsy syndrome?
At least two unprovoked (or reflex) seizures occuring more than 24 hours apart
Explain the difference between primary and secondary epilepsy- giving some examples of secondary causes of epilepsy
- Primary: unknown cause/idiopathic (~50-60%)
-
Secondary: known cause of epilepsy e.g.:
- Pre- or peri-natal injuries (e.g. hypoxia)
- Brain tumour
- Stroke
- Degenerative CNS conditions e.g. Alzheimers
- Infection
Epilepsy most commonly occurs in isolation however some conditions do have an association with epilepsy; state some
- Cerebral palsy (30%)
- Tuberous sclerosis
- Mitochondrial disease
- Neurofibromatosis
Which age groups(s) is epilepsy most common in?
- New cases of epilepsy are most common among children, especially during the first year of life.
- The rate of new cases of epilepsy gradually goes down until about age 10 and then becomes stable.
- After age 55, the rate of new cases of epilepsy starts to increase, as people develop strokes, brain tumors, or Alzheimer’s disease, which all can cause epilepsy.
Which age groups(s) is epilepsy most common in?
- New cases of epilepsy are most common among children, especially during the first year of life.
- The rate of new cases of epilepsy gradually goes down until about age 10 and then becomes stable.
- After age 55, the rate of new cases of epilepsy starts to increase, as people develop strokes, brain tumors, or Alzheimer’s disease, which all can cause epilepsy.
What investigations may you do for someone presenting with seizures?
- Blood glucose
- FBC
- U&Es
- Bone profile (for calcium)
- Toxicology screen
- Neuroimaging (head CT or MRI brain dependent on what suspecting)
- EEG (will only be abnormal during the seizure)
Outline the main aspects of management of epilepsy
-
Education surrounding epilepsy including:
- General day-to-day advice e.g. what they can & can’t do without supervision
- Advice regarding what to do during a seizure
- Management of status epilepticus
- Support groups
- Must inform DVLA if driver
- Pharmacological management/maintenance medication (most neurologists start after 2nd seizure though NICE specifies starting after first seizure if certain criteria are met)
-
Rescue medications (people will be given specific instructions on when to use these in their seizure action plan)
- Benzodiazepines
- E.g. buccal midazolam
- E.g. rectal diazepam
- Benzodiazepines
Anti-epileptic drugs often have more than one mechanism of action; true or false?
True
Anti-epileptic drugs can be sodium channel blockers; describe the mechanism of aciton of Na+ channel blockers in seizures
- Remember that Na+ channels open by depolarisation, allow Na+ in, then become inactivated and need hyperpolarisation to acitvate them and let them enter closed state. Depolarisation occurs and cycle starts again..
- Na+ channel blocker seizure durgs block Na+ channels when they are in the inactivated state
- This prevents the Na+ channel from recovering to the closed state and hence the open state so prevents further influx of Na+ through these channels (keeps channel in inactive state)
- Reduces depolarisation, reduces likelihood of threshold being reached therefore reduces neuronal transmission
State 3 examples of anti-epileptic drugs that are Na+ channel blockers
- Phenytoin
- Carbamazepine (trade name= tegretol)
- Lamotrigine
Lamotrigine is primarily a Na+ channel blocker (hence we have classed it as one) but it may also affect calcium channels; true or false?
True
Blocks Ca2+ channels which prevents calcium influx and hence prevents vesicles fusing with membrane to release neurotransmitter
Describe the mechanism of action of levetiracetam (trade name Keppra)
- Binds to glycoproteins on synaptic vesicles
- Stops release of of neurotransmitter
- Hence reduces neuronal activity
Discuss which antiepileptics are used first and second line for the different types of seizures
General rule: sodium valproate is first line for most forms of epilepsy (except focal seizures)
For sodium valproate, discuss:
- ADRs
- Contraindications
- Interactions (don’t worry about too much)
- If any monitoring is required
ADRs
- Increased appetite & weight gain
- Hair loss/alopecia
- Tremor
- Hepatitis
- Pancreatitis
- Thrombocytopenia
- Teratogenic (neural tube defects)!!!!
Contraindications
- NICE state should not use in women of child-bearing age unless there are no suitable alternatives & strict criteria are met to ensure they don’t get pregnant (pregnancy prevention programme)
- Personal or family history severe hepatic dysfunction
Interactions
- Lots of interactions. Some to note are meropenem decreases concentration of sodium valproate
Any monitoring required
- Liver function tests (LFTs, coagulation) both prior to starting and during first 6 months
- FBC (looking particularly at platelets) prior to starting
For carbamezapine, discuss:
- ADRs
- Contraindications
- Interactions (don’t worry about too much)
- If any monitoring is required
ADRs
- Dizziness
- Drowsiness
- Visual disturbances (particularly diplopia)
- Weight gain
- SIADH
- Agranulocytosis
- Aplastic anaemia
Contraindications
- AV conduction abnormalities (unless paced)
- Hx bone marrow depression
Interactions
- P450 enzyme inducer hence LOTS of reactions
Any monitoring
- FBC, LFTs & U&Es recommended
- Measure plasma concentration after 1-2 weeks
For lamotrigine, discuss:
- ADRs
ADRs
- Stevens-Johnson syndrome
- Leukopenia
- Drowsiness
- Tremor
For phenytoin, discuss:
- ADRs
- Interactions (don’t worry about too much)
- If any monitoring is required
ADRs
- Drowsiness
- Gingival hyperplasia
- Peripheral neuropathy
- Vit D & folate deficiency
- Megaloblastic anaemia (folate deficiency)
- Osteomalacia (vit D deficiency)
Interactions
- P450 inducer so lots of interactions; some ones to note are:
- DOACs- Apixaban, rivaroxaban, edoxaban, dabigatran (decrease exposure to the anticoagulants/make less effective)
- COCP (decreases effectiveness)
Monitoring
- Plasma concentration (to check within therapeutic level)
- FBCs
What is the DVLA guidance for pts with epilepsy?
General rule:
- Following a one-off seizure, can’t drive for 6 months if there are no relevant structural abnormalities on brain imaging and no definitive epileptiform activity on EEG (if there is, duration will be increased to 12 months)
- Following an epileptic seizure or multiple unprovoked seizures, can’t drive for 12 months (some situations in which it can be 6 months such as if doctor changed or reduced medication)
- Following a provoked seizure, must not drive and must inform DVLA and await their instructions (usually 6 months)
For ethosuximide, discuss:
- ADRs
ADRs
- Hiccups
- Night terrors
- Rashes
- Weight loss
- SJS
Why does phenytoin require close monitoring?
Exhibits zero order kinetics
A diagnosis of epilepsy can have a huge impact on life… state some examples of things a patient may not be able to do with a diagnosis of epilepsy
- Drive *NOTE: it is patient’s responsibility to inform DLA
- Swim
- Have a bath
- May have time off school/university/work
- Careful crossing roads or doing anything as could have seizure
Can women taking antiepileptics breastfeed?
Varies dependent on medication, BNF implies following are okay:
- “Carbamazepine probably too small to be harmful”
- “Small amounts in mothers taking phenytoin, not considered to be harmful”
- “Present in milk, but limited data suggest no harmful effect on infant.”
Summary of antiepileptic medications from passmed
Define status epilepticus
- Single seizure lasting > 5 minutes OR
- 2 or more seizures within a 5 minute period without the person returning to normal in between
Discuss the management of status epilepticus
-
A-E assessment including:
- Secure airway (may need adjunct)
- High flow oxygen
- IV access
- Bloods
- Check glucose
-
First line= benzodiazepines
- In hospital, IV lorazepam 4mg. Can be repeated after 10 minutes if continues. (Could also give 10mg IM midazolam if cannot get IV access)
- In community, buccal midazolam or PR diazepam
- If continues, repeat benzodiazepines
- If continues, IV phenytoin or phenobarbital
- If still going after 30 mins, need ITU to anaesthetise with thiopentone and ventilate
State some advantages of levetiracetam (trade name Keppra)
- Generally well tolerated
- Safe in pregnancy
State some generic side effects of all anti-epileptic drugs
- Tiredness/drowsiness
- Nausea & vomitting
- Mood changes & suicidal ideation
- Osteoporosis (particularly in elderly)
- Rashes (this can include Steven Johnson syndrome- most likely in carbamezapine or phenytoin)
- Anaemia
- Thrombocytopenia
- Bone marrow failure
State two anti-epileptic drugs which may decrease effectiveness of some antibiotics
- Carbamezapine
- Phenytoin
Why will patients on anti-epileptics and warfarin require close monitoring?
Antiepileptics can cuase thrombocytopenia so with warfarin aswellt here is increase risk of bleeding
Patients on antiepileptic drugs can consume alcohol; true or false
Ideally patients should NOT consume alcohol
State two anti-epileptic drugs which decrease effectiveness of oral contraceptive pills
- Carbamezapine
- Phenytoin
When determining whether a patients AED is effective what is the main thing we ask about/focus on?
Seizure frequency
What antiepileptic drug can increase plasma concentration of other antiepileptic drugs?
Sodium valporate
What blood test, if raised, favours a diagnosis of a true epileptic seizure over a Pseudoseizures?
Prolactin
*why prolactin is raised following seizures is not fully understood. It is hypothesised that there is spread of electrical activity to the ventromedial hypothalamus, leading to release of a specific prolactin regulator into the hypophyseal portal system
Passmed summary of antiepilpetics
